tbuckley/cabot-search huggingface dataset:
Abstract 15332: Post-Resuscitation Epinephrine Infusion Restores Blood Pressure but Not Blood Flow in a Rat Model of Severe Pediatric Cardiac Arrest
Authors: Hoai Ton, Victor velado, Michael Shoykhet
Journal: Circulation (2022)

Introduction: In children resuscitated from cardiac arrest (CA), post-arrest hypotension occurs often and worsens outcomes. Continuous infusion of epinephrine (Epi) is the 1st-line treatment for post-arrest hypotension but may worsen organ perfusion due to vasoconstriction. Hypothesis: Epi infusion after resuscitation from pediatric asphyxial CA restores blood pressure but not organ perfusion. Methods: Immature rats (PND18-22, n=34) underwent 11.5 minutes of asphyxial CA followed by resuscitation. Rats with hypotension (mean arterial pressure (MAP)&lt;80% baseline) after resuscitation received infusions of either 0.9% NaCl (NS) or Epinephrine (Epi). MAP, carotid and femoral arterial blood flows (Fc, Ff) and renal oxygen tension (PrO2) were recorded. Results: One hour after resuscitation, MAP, Fc and Ff were 61.73 ± 2.68; 42.58 ± 3.84; and 19.53 ± 7.00 % of baseline, respectively. Epi infusion increased MAP in a dose-dependent manner, reaching 95.13 ± 7.93 % of baseline at 0.5 μg/kg/min. In contrast, Epi infusion up to 0.5 μg/kg/min increased Fc only to 49.55 ± 6.49 and Ff to 53.28 ± 7.13 % of baseline. NS infusion at equivalent volume had a more salutary effect than Epi on improving blood flow (Fc 64.62 ± 6.64 and Ff 60.25 ± 7.60 % of baseline). PrO2 reached 100% of baseline with Epi infusion and inspired O2 fraction (FiO2) = 1. However, at FiO2 = 0.21, Epi failed to restore PrO2 which reached 42% of baseline. Interestingly, a single 10 cc/kg NS bolus increased PrO2 to 100% of baseline at all FiO2 tested. Conclusions: In this rat model of severe pediatric asphyxial CA and resuscitation, post-resuscitation Epi infusion failed to restore carotid and femoral arterial blood flow despite normalizing blood pressure. Furthermore, Epi infusion restored neither renal perfusion nor oxygenation. In contrast, infusion of NS at comparable volumes was more effective than Epi at normalizing carotid and femoral blood flows as well as renal oxygenation. If validated in a large animal model, these results may indicate that Epi infusion after CA resuscitation contributes to organ injury and morbidity in children.
Abstract 15595: Whole Genome Sequencing to Identify Predictors of IVIG Response in Kawasaki Disease
Authors: Sadeep Shrestha, Howard Wiener, Hidemi Kajimoto, vinodh srinivasasainagendra, Dolena Ledee, Sabrina Chowdhury, Mikayla Beckley, Luz Padilla, Nagib Dahdah, Hemant K Tiwari, Michael A Portman
Journal: Circulation (2022)

Introduction: Kawasaki Disease (KD) leads as a cause of acquired cardiovascular disease among children in developed countries. Around~20% of patients are refractory to high-dose intravenous immunoglobulin (IVIG), the standard treatment, and are at high risk of developing coronary artery aneurysms. Hypothesis: Whole genome sequencing (WGS) will identify specific predictors of non-response and inform the mechanism of IVIG action. Methods: KD patients were diagnosed by the American Heart Association and the American Academy of Pediatrics (AHA/AAP) criteria and treated by AHA guidelines. IVIG refractoriness was defined by persistent or recurrent fever (&gt;38C)&gt;36 hours after completing infusion. We performed a case-control study with WGS on DNA from saliva or blood from 107 responders versus 103 non-responders. After processing informatics using the pipeline of Genome Analysis Toolkit (GATK), additive genetic models were assessed for all common variants using logistic regression. We adjusted for age, gender, and race based on principal components. We also conducted SNP-set (Sequence) Kernel Association Test (SKAT) with common and rare variants in the gene regions with the most statistically significant SNP results. Results: Average sequencing depth was 30x and with a total of 34,548,910 variants. While SNPs in genes previously indicated in the IVIG pathway were confirmed, multiple novel SNPs in various gene regions were also statistically significant (often p&lt; 10-6; Figure-Manhattan plot). SKAT analysis suggested joint effects of multiple SNPs in individual gene regions. Conclusions: We confirmed SNPs in genes from previous reports and identified multiple novel ones, indicating plausible previous unsuspected IVIG mechanisms pathways. Potentially, functional disruption of these genes could lead to non-response. Further, a panel of these SNPs can be a prognostic tool for identifying at-risk KD patients that require therapy intensification.
Abstract 15281: Patient and System-Related Delays in Presentation and Invasive Coronary Angiography in Patients Presenting With Acute Myocardial Infarction Secondary to Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry
Authors: Dharam J Kumbhani, Esther S Kim, Malissa Wood, Katherine Leon, Gerald C Chi, Anna Grodzinsky, Heather L Gornik, Bryan Wells, Jennifer Lewey, Angela Taylor, Daniella Kadian Dodov, Connie N Hess, Stanislav Henkin, Kathryn Lindley, Gretchen Morris, James L Orford, Lori Tam, Samuel Norris, Cassandra Reyes, Fahad Alkhalfan, Clara Vitarello, Laurette Femnou Mbuntum, sahar naderi
Journal: Circulation (2022)

Introduction: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome especially in young patients. Factors associated with delays in presentation and care delivery are not well understood. Methods: We used data from the iSCAD Registry which is a prospective multicenter US registry of patients with SCAD. Early vs. delayed hospital presentation (&lt; 24 vs. ≥ 24 hours), and early vs. delayed coronary angiography (time from hospital presentation to coronary angiography &lt; 24 vs. ≥ 24 hours) for SCAD patients with AMI were assessed. Patient characteristics, and in-hospital events were compared between the two groups. Factors associated with delayed presentation and angiography were explored using multivariable logistic regression. Results: A total of 346 SCAD (294 white, 52 non-white) patients presented with STEMI (34%) or NSTEMI; 57 had a delayed presentation to the hospital after symptoms onset. No significant factors were identified for delays in seeking care. However, white race was less likely to have delayed invasive coronary angiography (multivariable OR=0.38; 95% CI 0.19 to 0.76; p=0.0059). Patients undergoing delayed angiography were also more likely to be medically managed (91.7% vs. 69.8%, p=0.0008), but less likely to receive dual antiplatelet therapy (57.0% vs. 73.1%, p=0.007). In-hospital outcomes were similar between the two groups. Conclusion: In this study, no patient-related variables were identified that predicted a delay in presentation with AMI secondary to SCAD. On the other hand, non-white race was associated with delays in performing invasive coronary angiography. Further investigation is required to determine the factors contributing to this potential disparity.
Abstract 15252: Impact of Atrial Fibrillation on Patients With Carcinoid Syndrome: A National In-Patient Sample Analysis
Authors: Akhilesh Babbili, Sahith Reddy Thotamgari, Udhayvir Grewal, Anuj Thakre, Paari Dominic
Journal: Circulation (2022)

Introduction: Carcinoid heart disease is one of the major causes of mortality in patients with carcinoid syndrome. Although right-sided valvular dysfunction is well studied in carcinoid heart, there are limited data on the impact of atrial fibrillation (AF) on in-hospital mortality in these patients. We sought to assess the in-hospital outcomes in patients with carcinoid syndrome and a concurrent diagnosis of AF. Methods: We analyzed the National Inpatient Sample database from January 2016- December 2018 to identify hospitalizations for Carcinoid syndrome using the ICD 10 CM code E34.0. Study cohort was further divided into patients with and without AF. Chi-square test and multivariate logistic regression were used to analyze the association. All statistical analyses were performed using weighted values. Results: During the study period, 9320 hospitalizations with carcinoid syndrome were identified. Among these, 1430 (15.3%) had atrial fibrillation. Baseline characteristics and outcomes are shown in table 1. Patients with AF were older (71.8±9.8 vs 63.4±13.6, p&lt;0.001) and had a higher Elixhauser comorbidity index (21.5±6.6 vs 17.6±6.5, p&lt;0.001). AF is noted to be associated with significantly higher in-hospital mortality (OR 2.0, 95% CI 1.6-2.5, p&lt;0.001), and respiratory failure requiring mechanical ventilation (OR 1.9, 95% CI 1.5-2.5, p&lt;0.001). After adjusting for age, sex, race, and significant baseline comorbidities, AF was independently associated with higher in-hospital mortality (aOR 1.64, 95% CI 1.3-2.1, p&lt;0.001*) and mechanical ventilation (aOR 1.88, 95% CI, 1.4-2.5, p&lt;0.001*) Conclusions: Atrial fibrillation is associated with significantly higher in-patient hospital mortality and mechanical ventilation in patients with carcinoid syndrome. Further longitudinal observational studies are needed to validate these findings.
Abstract 15282: COVID-19 Cases, Hospitalizations, and Vaccination Among Adults With Congenital Heart Disease
Authors: Matthew Oster, Romie N Velani, J'Neka S Claxton, Kristina W Kuo, Osamah Aldoss, Charles E Canter, Mansi Gaitonde, Anitha John, gurumurthy H Malikarjun, Kimberly McHugh, David M Overman, Geetha Raghuveer, Logan Spector, Lazaros Kochilas
Journal: Circulation (2022)

Background: There are conflicting data as to whether congenital heart disease (CHD) should be considered a condition that places a person at high risk of severe illness from COVID-19. The objective of our study was to compare COVID-19 cases, hospitalization rate, and vaccine uptake among adults with history of cardiac intervention vs. the general US adult population. Methods: We performed a cross-sectional study of adults using survey data from the Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE). This survey, conducted in 2021-2022, queried CHD survivors regarding a variety of domains, including history of COVID-19 infection and vaccination. Adults with a history of surgical, catheter, or electrophysiologic intervention at 1 of 8 Pediatric Cardiac Care Consortium centers were eligible for inclusion. Results were limited to those aged 18-49 years to allow comparison to age-specific data from the US Centers for Disease Control and Prevention. Results: Among 1,277 respondents (20.2% response rate), the median age was 32 years (IQR: 27-38 years), the majority were female (55.6%), and the most common race/ethnicity was Non-Hispanic White (89.9%). There was no difference in history of a positive COVID-19 test in persons with CHD compared to adults of a similar age (26.8% vs 28.1%, p=0.86). However. those with CHD and COVID-19 were significantly more likely to require hospitalization than adults in the general population with COVID-19 (1.75% vs. 0.26%, p=0.004) (Figure). Regarding COVID-19 vaccination, 76.5% of CHD PULSE respondents reported a history of at least 1 COVID-19 vaccine, with no differences vs. the general population when compared by age (p=0.99). Conclusions: Given higher hospitalization rates among adults with CHD and COVID-19, CHD should be considered a medical condition that places one at increased risk of severe COVID-19. These findings underscore the importance of COVID-19 vaccination in this population.
Abstract 15728: Apixaban Use in Patients Supported by Durable Left Ventricular Assist Device
Authors: Mark S Slaughter, Siddharth Pahwa, Stephanie Moore, Rohan Samson, Devan Costelle, Jaimin Trivedi
Journal: Circulation (2022)

Introduction: Coumadin is currently the standard of care for long-term anticoagulation in patients supported with a left ventricular assist device (LVAD). Coumadin requires frequent testing and is associated with adverse events. The aim of this study was to evaluate the routine use of Apixaban in contemporary LVAD patients. Methods: A single center LVAD database was retrospectively queried to identify HeartMate 3 (HM3) patients between January 2016 and May 2022. Patients were divided into 2 groups based on anticoagulation received: Coumadin vs Apixaban. The primary outcome was 1-year mortality and secondary events of freedom from bleeding and stroke at 1 year. Univariate statistics and Kaplan-Meier curves were used for data analysis. Results: A total of 67 consecutive patients underwent HM3 implant during the study period: 20 (30%) coumadin and 47 (70%) apixaban. There was no difference in gender, age, BMI, creatinine, previous stroke or INTERMACS level between groups (Tabe1). Total days of support: Coumadin 25,750 days and Apixaban 16,556 days. The mortality at one year was comparable (5% v. 6%, p=0.12). The coumadin group had higher overall bleeding events (55% v. 17%, p&lt;.01) and freedom bleeding at 1 year was better in apixaban group (86% v. 64%, p=0.04). Freedom from stroke at 1 year was comparable between the groups (95% v. 97%, p=026). Survival at 1 year with no stroke or bleeding was similar (Figure 1). Conclusion: In this single center retrospective analysis, Apixaban in patients with a durable LVAD has shown reduced bleeding events and comparable stroke and survival outcomes. This early experience demonstrates that Apixaban is a possible alternative to Coumadin.
Abstract 15023: Minimum Electrode Spatial Resolution for Arrhythmia Rotor Detection and Localization
Authors: Maria Ines Gandara, Kedar K Aras, Igor Efimov
Journal: Circulation (2022)

Introduction: Efficacy of electrotherapy or ablation therapy for treatment of arrhythmias is dependent on accurate detection of arrhythmia focal or reentrant drivers. However, success rates have been inconsistent, with frequent arrhythmia recurrence. A likely reason is the limited current spatial resolution of mapping devices, which averages 4 mm. The goal of this study was to determine the minimum spatial resolution necessary to identify and localize arrhythmia reentrant drivers (rotors). Methods: We conducted dual-sided (epicardial and endocardial) optical mapping studies in 12 donor human right ventricular wedge preparations subjected to arrhythmia induction protocol (S1S1 restitution and/or 50Hz burst pacing). The resulting arrhythmia data (0.7mm spatial resolution) was down sampled to different spatial resolutions (1.4-7mm) and up sampled back to full resolution. Rotors were tracked for each sub-resolution and compared to the rotors in the original data. Further comparisons were made according to arrhythmia type, sex, anatomical region, and mapped surface. Results: Rotor detection accuracy for currently used mapping devices was found to be 57±4%. Localization accuracy was 61±7%. For the current average spatial resolution, clinical rotor detection and localization accuracies can be expected to fall within a confidence interval of 47-67% and 46-75%, respectively. For the spatial resolutions tested, detection accuracy was above 80% only for a resolution of 1.4 mm, while localization accuracy reached that value at 2.1 mm. Moreover, the arrhythmia type affected detection and localization accuracies, which decreased consistently with loss of spatial resolution for unstable arrhythmias and had steadier values for stable arrhythmias. When comparing mapped surfaces, rotor incidence was higher in the endocardium, likely due to the presence of adipose tissue on the epicardial surface. Differences in sex and anatomical region had no statistically significant impact. Conclusions: The spatial resolution of current devices is insufficient to map rotors accurately, especially for unstable arrhythmias. For both detection and localization accuracies to be above 80%, a resolution of at least 1.4 mm is required.
Abstract 15288: The Use of Cha2ds2-vasc Score to Predict Functional Outcomes of Mechanical Thrombectomy
Authors: James Livesay, Benjamin Fogelson, Shawna Stevens, Chirag Patel, Hassan Tahir, William Dieter, Brian Wiseman, Raj Baljepally
Journal: Circulation (2022)

Introduction: Mechanical thrombectomy is a widely used form of revascularization for ischemic strokes secondary to large vessel occlusions. Functional outcomes are typically assessed following mechanical thrombectomy using the modified Rankin scale. CHA 2 DS 2 -VASc score is commonly used to estimate the stroke risk of patients with atrial fibrillation, but there are a plethora of studies showing it can be used in various situations. Our study aimed to assess the utility of CHA 2 DS 2 -VASc score in predicting outcomes of patients undergoing mechanical thrombectomy. Methods: We performed a single center, non-randomized, retrospective study. The study included 448 patients that underwent mechanical thrombectomy for large vessel occlusion strokes. CHA 2 DS 2 -VASc score was calculated on each patient and the study population was divided into 3 groups based on CHA 2 DS 2 -VASc score (Score ≤ 2, Score 3-4 and Score ≥ 5). Association between CHA 2 DS 2 -VASc score and 90-day modified Ranking score and in-hospital, 30-day, and one year mortality was evaluated and compared between the three groups. Results: A total of 312 patients met criteria for the study. Patients in the high risk CHA 2 DS 2 -VASc score had a significantly higher modified Rankin score (4.48) when compared to low (2.57) and intermediate (3.82) groups (Image 1). Higher CHA 2 DS 2 -VASc scores were also associated with a significantly higher in-hospital, 30-day, and one year mortality. Conclusion: CHA 2 DS 2 -VASc score can predict worse functional and survival outcomes in patients undergoing mechanical thrombectomy for a large vessel occlusion. CHA 2 DS 2 -VASc score ≥ 5 was associated with higher modified Rankin score and mortality.
Abstract 15014: Aberrant, Elevated Papillary Muscle and Left Ventricular Wall Forces Associated With Mitral Valve Prolapse Are Normalized by Surgical Neochordal Repair but Not by Transcatheter Edge-to-Edge Repair
Authors: Matthew H Park, Antonia Van Kampen, Yasufumi Nagata, Yuanjia Zhu, Pearly Pandya, Michael A Borger, Y. Joseph J Woo
Journal: Circulation (2022)

Introduction: Recent studies have linked mitral valve prolapse (MVP) to localized myocardial fibrosis and ventricular arrhythmia, and early imaging work has shown altered ventricular motion with papillary muscle (PM) traction in MVP and MitraClip patients. We aimed to biomechanically compare MitraClip and neochordal repair for MVP on PM forces ex vivo . Methods: We developed a force transduction system to measure the forces exerted on the PMs throughout the cardiac cycle in a left heart simulator ( Fig A ) with consistent pressures. Using a randomized, paired procedure with porcine MVs (n=4), we measured the hemodynamics and forces for control, diseased (P2 prolapse via chordal rupture), MitraClip repair ( Fig B, C, D ) (single P2 clip), and neochordal repair (P2 primary neochord on each PM) conditions. Results: We found that MitraClip PM forces (7.19 ± 0.31 N) are higher by 9.34% compared with those of controls (6.58 ± 0.21 N, p&lt;0.001 ). This result is similar to MVP valves modeled by superior PM displacement, which showed 9.23% higher forces than those of controls (n=10, p&lt;0.001 ). Moreover, MitraClip repaired valves showed PM force increases of 6.4% compared with forces of neochordal repair (6.76 ± 0.22 N, p&lt;0.001 ), despite having similarly reduced regurgitation fractions (5.05% ± 1.98% vs. 4.25% ± 1.51%, respectively, p&gt;0.05 ) compared with those of the diseased state (16.96% ± 3.04%, p&lt;0.001 ) and controls (2.66% ± 0.87%). Additionally, neochordal repair valves had 2.79% higher forces compared to those of control valves ( p&lt;0.001 ). Conclusions: We discovered that MitraClip, while reducing regurgitation, does not restore aberrant forces on the PM induced in MVP to baseline or reduced levels, while neochordal repair does. Our work suggests that these elevated forces, associated with MVP and MitraClip, predisposes the MV to continued traction, which may present a long-term harm to patients by catalyzing localized fibrosis and ventricular arrhythmia.
Abstract 15006: Imaging the Mitochondrial Nucleoid Body in Pulmonary Arterial Hypertension Reveals Changes in Nucleoid Body Distribution and Composition in Human Pulmonary Artery Smooth Muscle Cells
Authors: Jenna A Rossi, Kimberly J Dunham-Snary, Jeffrey D Mewburn, Stephen L Archer
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) exhibits excessive proliferation of pulmonary artery smooth muscle cells (PASMC). This is related to mitochondrial abnormalities, including a metabolic shift to aerobic glycolysis, and increased mitochondrial fragmentation. Mitochondrial DNA (mtDNA) encodes 13 proteins critical to mitochondrial function and is supported by multi-protein complexes called nucleoid bodies (NB) comprised of key mtDNA maintenance proteins. Previous data shows increased mtDNA damage and increased NB protein levels in PAH vs control PASMC. This seems to suggest an attempted compensatory response to mtDNA damage in PAH. We aim to identify NB composition and distribution changes in PAH. We hypothesize that NB structure and distribution throughout the mitochondrial network are dysregulated in PAH. Methods: NBs were visualized in control and PAH PASMC (n=15 per group). Cells were loaded with MitoTracker Deep Red (mitochondrial matrix dye) and visualized using stimulated emission depletion (STED) microscopy. We simultaneously imaged mtDNA and NB proteins TFAM, POLG and SSBP. NB protein distribution was quantified by comparing the rates of mtDNA-protein interactions per mitochondrial area. Results: On visualization of PASMC, mitochondrial fragmentation was evident in PAH vs control. Qualitative findings in PAH PASMC included increased heterogeneity of NB size (diameter) and spatial distribution in PAH compared to control. IF quantitation showed decreased mtDNA/cell (193±20 vs 326±28 mtDNA/cell, p&lt;0.05) and increased SSBP (0.91±0.07 vs 0.59±0.37 SSBP/mtDNA, p&lt;0.05) in PAH cells. These results are consistent with previous findings. Conclusion: These findings suggest a compensatory remodeling of NB in PASMC and is an important step in characterizing the NB shape, distribution, and composition in PAH. These findings will direct experiments analyzing gene and protein expression to further elucidate the role of NB in PAH.